J Psychopharmacol

Starting benzodiazepines or Z-drugs linked to long-term substance-related risks

October 7, 2025

Study details: This Swedish nationwide matched cohort study followed 960,430 individuals initiating benzodiazepine or Z-drug (BZDR) therapy between 2007–2019, all without prior substance-related conditions. Each BZDR recipient was matched 1:1 to a non-recipient. A co-twin comparison (n=12,048 pairs) was also conducted to control for genetic and familial confounding. Outcomes included substance use disorders, poisoning, deaths, and related criminal offenses, tracked over up to 14 years using flexible parametric survival models.

Results: BZDR initiation was associated with significantly increased risks of alcohol- and drug-related problems. Incidence rates per 1,000 person-years were 5.60 vs. 2.79 for alcohol-related and 4.15 vs. 1.23 for drug-related problems in recipients vs. non-recipients. Adjusted hazard ratios were 1.56 (95% confidence interval [CI], 1.53–1.59) for alcohol-related and 2.11 (95% CI, 2.05–2.17) for drug-related outcomes. These associations persisted across all sensitivity analyses, including co-twin comparisons.

Clinical impact: The findings underscore the need for cautious prescribing of BZDRs, especially in patients with potential vulnerability to substance use. Clinicians should monitor for emerging substance-related issues post-initiation and consider alternative therapies when appropriate.

Source:

Wang X, et al. (2025, October 1). J Psychopharmacol. Incident benzodiazepine and Z-drug use and subsequent risk of alcohol- and drug-related problems: A nationwide matched cohort study with co-twin comparison. https://pubmed.ncbi.nlm.nih.gov/41035208/